The effects of adolescent drug use on cognitive functioning is a significant public health concern. Adolescence marks a time of considerable neural development, particularly in brain regions that control attention and behavioral impulses. Drug use during these critical periods of brain development could impede or alter the normal course of neural maturation, resulting in long-term cognitive deficits in these areas. There is also considerable interest in the possibility that stimulant medications, such as methylphenidate, used in the treatment of attention deficit hyperactivity disorder (ADHD), could sensitize adolescents to the rewarding and disinhibiting effects of other stimulants, thus increasing their risk of abuse as this population enters young adulthood. Despite growing concern about the consequences of adolescent drug use, little is known about the specific behavioral and cognitive deficits that might result from a history of adolescent drug use. The proposed R21 project is designed to identify specific inhibitory-based, neurocognitive deficits associated with a history of adolescent drug use and to examine how this association is mediated by two established adolescent risk factors for substance abuse, ADHD and conduct disorder (CD). Inhibitory deficits will be examined in two domains of functioning: control of behavioral impulses and the ability to select attention to relevant stimuli. Studies will use behavioral and psychophysiological techniques (EEG) to identify specific inhibitory deficits prior to, and following, a history of adolescent drug use. Drug challenge tests are also proposed to identify potential differences in the acute sensitivity to the neurocognitive and rewarding effects of abused drugs as a function of adolescent drug use history and adolescent history of ADHD and CD. The long-term objective of this research is to distinguish antecedent inhibitory deficits that contribute to risk of early-onset adolescent drug use, from resultant inhibitory deficits that represent the underlying neurological insult following a protracted history of adolescent drug use.